The field of the invention is systems and methods for magnetic resonance imaging (“MRI”). More particularly, the invention relates to phantoms for use in calibrating MRI techniques for quantifying fat concentration, iron concentration, or both.
The ability to quantify fat concentration in the body has become increasingly important given the high prevalence of obesity and obesity-related comorbidities. Likewise, the ability to quantify iron concentration in the body is important for monitoring phlebotomy treatment effectiveness in patients with hemochromatosis, and monitoring chelation treatment effectiveness in patients who receive routine blood transfusions (i.e., hemosiderosis). Further, fat and iron often coexist in organs such as the liver, pancreas, and bone marrow. MRI-based techniques for the quantification of fat and iron concentration in tissue have experienced rapid development over the past decade. Validation of these techniques is an essential prerequisite to their widespread clinical translation.
Phantoms are devices that are placed in the bore of an MRI system to test or calibrate its operation. Phantoms may be made of materials having known magnetic resonance properties or they may contain cavities filled with such materials. The MRI system is operated with the phantom in place to produce a spectrum or an image from which proper operation of the MRI system may be determined.
More particularly, phantoms are used in research studies and for quality assurance and calibration in clinical studies. Using these phantoms enables highly controlled validation of the accuracy, precision, and reproducibility of MRI systems and techniques. However, current phantom designs for fat and iron do not accurately replicate the magnetic resonance signal behavior that is observed in vivo, and thus the currently available phantoms are not useful for the validation of MRI-based fat and iron quantification techniques.
Techniques for fat and iron quantification are typically based on the acquisition of chemical shift-encoded magnetic resonance signals. Using these acquired signals, fat and water signal components can be separated based on their different resonance frequencies, and iron concentration can be estimated based on the transverse relaxation rate, R*2. In general, R*2 is the rate of decay of the water and fat signals, which is accelerated by the presence of iron in tissue due to the introduction of microscopic magnetic field inhomogeneities.
Traditionally, water-fat phantoms have been constructed using emulsions of deionized water and oil. Alternatively, iron concentration phantoms have usually been constructed by dissolving different concentrations of superparamagnetic iron oxide (“SPIO”) nanoparticle contrast agents in water. Other paramagnetic substances (e.g., manganese chloride) have also been used to mimic the effects of iron on magnetic resonance signal relaxation rates. These constructions are often built as agar gels to prevent separation of the different components. Other substances are often added to the phantoms to better replicate in vivo signal behavior (e.g., sodium chloride or cupric sulfate), to maintain the oil-water emulsion (e.g., sodium dodecyl sulfate), as well as to increase the shelf-life of the phantoms (e.g., sodium benzoate, sodium azide).
As mentioned above, previous attempts at constructing water-fat-iron phantoms have been based on mixing prescribed amounts of deionized water, oil, and superparamagnetic iron oxide (“SPIO”) nanoparticle contrast agents to achieve the desired fat and iron concentrations. From a composition perspective, these phantoms accurately reflect the materials of interest from which in vivo tissues are composed. However, from a magnetic resonance signal perspective, a significant discrepancy is observed in the behavior of these phantoms versus that observed for in vivo tissue. In particular, MRI experiments have demonstrated that these phantoms exhibit a dual-R*2 behavior (i.e., the water components and the fat components have different R*2 signal decay rates), whereas in vivo liver experiments have demonstrated a single-R*2 behavior in the liver tissue in the presence of iron (i.e., both water and fat have very similar R*2 signal decay rates). This discrepancy makes currently available water-fat-iron phantoms inadequate for validating quantitative imaging techniques because the signal behavior observed in the phantoms does not match the signal observed in vivo for tissues such as liver.
Currently available water-fat-iron phantoms are therefore not reliably accurate. As clinicians begin adopting use of MRI techniques for fat and iron quantification, there will be a larger need for an accurate calibration and quality assurance phantoms.